AB1135 RESPONSE TO SARS-COV-2 VACCINATION IN SYSTEMIC AUTOIMMUNE RHEUMATIC DISEASE DEPENDS ON IMMUNOSUPPRESSIVE REGIMEN: A MATCHED, PROSPECTIVE COHORT STUDY
Authors: P. Mandl, S. Tobudic, H. Haslacher, D. Mrak, T. Nothnagl, T. Perkmann, H. Radner, J. Sautner, E. Simader, F. Winkler, H. Burgmann, D. Aletaha, S. Winkler, S. Blüml
Journal: Annals of the Rheumatic Diseases (2022)

Background Vaccination efficiency has been demonstrated to be reduced in patients with systemic autoimmune rheumatic disease (SARD) compared with the general population. Objectives To assess the humoral response to mRNA vaccine in patients with (SARD) and the effect of immunosuppressive medication in a matched cohort study. Methods Patients with SARD were enrolled and matched 1:1 for gender and age with healthy control subjects (HC). Differences in the humoral response to two doses of mRNA vaccine BNT162b2 in terms of seroconversion rate and SARS-COV-2 antibody titer between the two groups and impact of treatment within SARD patients was assessed using Fisher’s exact test, Student’s t-test, Mann-Whitney test and Kruskal-Wallis test, adjusting for multiple testing. Results We enrolled 82 patients with SARD and 82 matched HC (Table 1). Among patients the seroconversion rate was significantly lower after the 1st dose (65% compared to 100% in HC, p&lt;0.0001) but levelled up after the 2 nd dose (94% vs. 100%). While the difference in seroconversion rate was independent of treatment regime (no disease modifying anti-rheumatic drug (DMARD), DMARD monotherapy, DMARD combination therapy), the seroconversion rate of SARD patients on mono- or combination DMARD therapy was also significantly lower as compared to those receiving no DMARD therapy (56% for monotherapy and 57% for combination therapy compared to 77% for no DMARD therapy, p=0.002 and p=0.004 respectively; Figure 1A). Seroconversion rate after the 2 nd dose was significantly lower for patients on combination DMARD therapy compared to all other groups (81% compared to 95% for monotherapy, and 100% for both no DMARD therapy and HC respectively, all p&lt;0.0001); also antibody titers after the 2 nd dose were lower when comparing patients on combination DMARD therapy to all other groups (49 binding antibody units (BAU)/ml versus 1673 BAU/ml in HC, p&lt;0.0001; 2500 BAU/ml in those on no DMARD therapy, p&lt;0.0001; and 687 BAU/ml in those on DMARD monotherapy, p=0.0072; Figure 1B). Considering effects of individual compounds, mycophenolate mofetil in mono- or combination therapy led to lower antibody titers after the 2 nd dose as compared to HC or patients receiving no DMARDs (2 BAU/ml versus 1673 BAU/ml and 2500 BAU/ml respectively, both p&lt;0.0001). Figure 1. Seroconversion rate (A) and anti-SARS-Cov 2 S antibody levels (B) after the 1 st and 2 nd vaccination between the healthy control (HC) group and patients according to therapy Table 1. Study subject characteristics SARD (n=82 ) HC (n=82 ) Age, mean (±SD) 52.05 (±14.06) 52.15 (±13.42) Female, n (%) 65 (79%) 65 (79%) Different disease entity, n (%): 33 (40%) Systemic lupus erythematosus Systemic sclerosis 13 (16%) Other connective tissue diseases* 15 (18%) Vasculitides# 17 (21%) Miscellaneous$ 4 (5%) Treatment groups, n (%): 43 (52%) csDMARD or b/tsDMARD monotherapy csDMARD and/or b/tsDMARD combination therapy 16 (20%) No therapy 23 (28%) Treatment agents, n (%): 13 (16%) Methotrexate Mycophenolate 14 (17%) Hydroxychloroquine 28 (34%) Azathioprine 13 (10%) Belimumab 3 (4%) Tocilizumab 3 (4%) Tacrolimus 2 (2%) Olumiant 1 (1%) *dermato-/polymyositis (n=4), mixed connective tissue disease (n=2), primary Sjögren’s syndrome (n=6), undifferentiated connective tissue disease (n=3) # antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (n=3), Behcet’s disease (n=1), large-vessel vasculitis (n=3), polymyalgia rheumatica (n=10) $ adult-onset Still’s disease (n=1), immune deficiency (n=2), sarcoidosis (n=1) b/tsDMARD: biological/targeted synthetic disease modifying antirheumatic drug; csDMARD: conventional synthetic disease modifying antirheumatic drug; HC: healthy control; n: number; SARD: systemic autoimmune rheumatic disease; SD: standard deviation; Conclusion Patients with SARD showed a good response after the 2nd vaccination with the mRNA vaccine. However, the choice of immunosuppressive regimen has a marked effect on both seroconversion rate and overall antibody titer. Acknowledgements We thank Sylvia Taxer and Zoltan Vass for their support. Disclosure of Interests Peter Mandl Speakers bureau: AbbVie, Janssen, Novartis, Consultant of: AbbVie, Janssen, Novartis, Grant/research support from: AbbVie, BMS, Lilly, Novartis, MSD, UCB, Selma Tobudic: None declared, Helmut Haslacher: None declared, Daniel Mrak: None declared, Thomas Nothnagl: None declared, Thomas Perkmann: None declared, Helga Radner Speakers bureau: Gilead, Merck Sharp, Pfizer, Abbvie, Consultant of: Gilead, Merck Sharp, Pfizer, Abbvie, Judith Sautner Speakers bureau: Otsuka, Novartis, Consultant of: Lilly, Astro Pharma, UCB, Abbvie, Elisabeth Simader Grant/research support from: Pfizer, Bristol-Myers Squibb, Florian Winkler: None declared, Heinz Burgmann: None declared, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Consultant of: Abbvie, Amgen, Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz , Grant/research support from: Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Stefan Winkler: None declared, Stephan Blüml Speakers bureau: Novartis, Abbvie, Consultant of: Gilead, Merck, Novartis, Abbvie